Communications
doi.org/10.1002/ejoc.202100501
2018, our group have revealed that isocyanide moieties can be
(entries 9–11). The loadings of photocatalyst were also consid-
ered as key parameters for the cascade reaction. When lower or
higher dosage of catalyst were used, no competitive yields
would be obtained (entries 12 and 13). It is worthy to mention
that the presence of oxygen might quench an excited photo-
catalyst intermediates[11] thus totally inhibiting the cascade
reactions either under air or oxygen atmosphere (entry 14). No
conversion could be observed for reactions in the dark or with
conventional heating (entry 15). The target product also can be
obtained with lower yield when we attempted to reduce the
amount of THF (1.0 mL) or use a cosolvent. The above results
collectively indicate that blue light, 4CzIPN, and nitrogen
atmosphere are all essential to achieve the cascade reaction.
After establishing the optimal conditions [1a (0.20 mmol),
4CzIPN (10 mol%) in 2 mL THF irradiated by 3 W blue LEDs for
24 h under N2 atmosphere], we subsequently started to explore
the substrate scope for the cascade cyclization reactions by
examining various isocyanides 1 and ethers 2 (Scheme 2).
Initially, isocyano-aryl thioethers attached with variety of func-
tional groups were selected to react with THF and 1,4-dioxane
under the optimal conditions. Both electron-rich groups (À Me,
À OMe) and electron-poor groups (À F, À Cl, À Br) were well
tolerated in the present reactions and smoothly led to the
corresponding products (3a–3k) in medium to good yields (42–
70%). Notably, halide substituent Br on both 4- and 5- positions
of the phenyl rings was found to be suitable in this trans-
formation (3e, 3g and 3l), although the former one giving
relatively low yields. Moreover, the synthetic application of this
methodology was further extended to 1,3-dioxolane, and a
variety of substituted isocyanides performed well to afford the
corresponding products in combined yields ranging from 57%–
65% (3m/m’–3p/p’). To be noted, the products gave certain
preferences of C2 selectivity with ratios of 2:1–3:1 over C4
position.
used as ideal radical acceptors in the process of radical C(sp2/
sp3)-S cleavage mediated by manganese salt or synthetic
oxidant (DTBP) (Scheme 1b).[9] Inspired by the aforementioned
studies on ether functionalization, we envisioned that ether
radicals generated from visible light irradiation would be ideally
compatible with the imidoyl radical formation and CÀ S
cleavage.[4f,8,9a] With our continuing interest in carbon-heteroa-
tom bond cleavage and radical-involved reactions,[10] we herein
disclosed a novel visible light-induced oxidant-free and metal-
free cascade cyclization of 2-isocyanoaryl thioethers with ethers,
providing an expeditious approach to access ether-functional-
ized benzo-thiazoles (Scheme 1c).
We commenced the exploration with (2-isocyano-
phenyl)(methyl)sulfane (1a) and THF (2a) as the model
substrates for optimizing reaction conditions. To our delight,
with eosin Y as a photocatalyst, the model reaction underwent
smoothly to deliver 2-(tetrahydrofuran-2-yl)benzo[d]thiazole
(3a) in 49% isolated yield after being irradiated by 3 W white
LEDs for 24 h under a nitrogen atmosphere. (Table 1, entry 1).
Spurred by this preliminary result, systematically screenings of
the conditions were performed to enhance the efficiency. Both
organic dyes and transition metal photo-sensitizers were tested
as photocatalysts, including rose bengal, fluorecein, Mes-Acr+,
rhodamine B, fac-Ir(ppy)3 and Ru(bpy)3Cl2, giving yields ranging
from 0–53% (Table 1, entries 2–7). When it came to 1,2,3,5-
tetrakis-(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN), the yield
of desired product 3a could be improved to 55% (Table 1,
entry 8). Moreover, the wavelength of light sources dramatically
affected the reaction efficiency. For instance, the reaction
irradiated by blue LEDs delivered target product in 66% yield,
green and red LEDs, however, were proved to be useless
On the other hand, the commonly used acyclic ethers were
further examined in this transformation. The reactions of
ethylene glycol diethyl ether with isocyanoaryl thioether and
other functionalized isocyanoaryl thioethers proceeded
smoothly to give the desired products in good yields (3q–3t,
48–60%). 1,2-Dimethoxyethane also reacted in the system but
impaired the efficiency a little furnishing 3u and 3v in 34% and
28% respectively. In addition, it was found that when the 2-
position of isocyanide is substituted by selenium, it can also
react with THF under the template reaction conditions to obtain
the target product 3w in 31% yield.
To gain further insight of the product-forming profile,
several mechanistic experiments were carried out (Scheme 3).
When radical scavengers of either TEMPO (2,2,6,6-tetramethyl-
1-piperidinyloxy) or BHT (2,6-di-tert-butyl-4-methylphenol) were
added into reaction mixtures under the optimized reaction
conditions, the cascade cyclizations were entirely inhibited. It
was indicated that the photo-induced THF radical was in-situ
quenched by TEMPO and BHT, which could be confirmed by
HR-MS analysis (eq. a, see details in the Supporting Informa-
tion). In order to capture more reaction intermediates, the
standard system was treated with tosylated diallylamine. As
shown in eq. b, THF radical, methyl radical and benzothiazole
Table 1. Visible
Light-Induced
Cascade
Reaction
of
(2-iso-
cyanophenyl)(methyl) sulfane with Ether: Conditions Screening.[a]
Entry
Photocatalyst
Light Source
Yield [%][b]
1
2
3
4
5
6
7
8
eosin Y
white LED
white LED
white LED
white LED
white LED
white LED
white LED
white LED
blue LED
green LED
red LED
49
0
0
50
0
53
13
55
rose bengal
fluorecein
Mes-Acr+
rhodamine B
fac-Ir(ppy)3
Ru(bpy)3Cl2
4CzIPN
9
4CzIPN
4CzIPN
4CzIPN
4CzIPN
4CzIPN
4CzIPN
4CzIPN
66
0
0
10
11
12
13
14
15
blue LED
blue LED
blue LED
blue LED
58[c]
60[d]
0[e], 0[f]
0[g], 0[h]
[a] Reaction conditions: 1a (0.20 mmol), 2a (2.0 mL) and 10 mol%
photocatalyst were irradiated by 3 W Blue LEDs (450-455 nm) under N2
atmosphere for 24 h at room temperature. [b] Isolated yield. [c] 5 mol%
4CzIPN. [d] 15 mol% 4CzIPN. [e] under oxygen atmosphere. [f] under air. [g]
°
in dark. [h] in dark and heated up to 50 C.
Eur. J. Org. Chem. 2021, 1–6
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